Essential fatty acids and fertility

Lipids are among the most important component of dairy cows’ diet. The high energy deriving from lipids, but most of all the dietary intake of specific fatty acids, have a positive impact on ovarian and reproductive function. They stimulate prostaglandin activity, steroid hormones synthesis from cholesterol, and insulin production.

Different feeds contain different lipids concentrations, mainly as triglycerides; they are absorbed at the intestinal level, after their hydrolysis into free fatty acids and glycerol by pancreatic lipases. Fatty acids are classified on the basis of their chain length and of the number of double bonds (unsaturation) in the molecule. If there is no unsaturation, they are defined as saturated fatty acids. Dietary fatty acids are both sources of energy (they enter the Krebs cycle to produce ATP) and fundamental constituents of biological membranes and several hormones and enzymatic systems.

As for amino acids, fatty acids are essential (only in the diet, they cannot be synthesized by the animal) or non-essential (both in the diet and synthesized). Linoleic (C18:2 n-6) and α-linolenic (C18:3 n-3) acid are essential for mammals. The number following the “n” represents the position of the first double bond, determined by counting the first methyl starting from the end of the carbon chain. N-3 means omega-3 (Ω 3), indicating an unsaturation at the third carbon starting from the end of the chain. The most important omega-3 polyunsaturated fatty acids (PUFA) are α-linolenic acid, stearidonic acid (C18:4 n-3), eicosatetraenoic acid (C20:4 n-3), eicosapentaenoic acid (EPA, C20:5 n-3), docosapentaenoic acid (C22:5 n-3), and docosahexaenoic (DHA, C22:6 n-3). EPA and DHA are non-essential because they can be synthesized starting from linolenic acid, but they are extremely important for cows’ health. Feeds with a high content of PUFA are fish, seaweed, while sunflower oil, soybean oil, and cotton are rich in linoleic acid. Linseed oil and fresh hay contain linolenic acid (Table 1).

Table 1: Fatty acids composition of feeds for monogastric and ruminants.

An omega-3 fatty acid cannot be transformed into an omega-6 one and vice versa. These PUFA can be part of membrane phospholipids or can be transformed into fatty acids with longer carbon chains or into eicosanoids, such as prostaglandins and leukotrienes. For example, arachidonic acid derives from linoleic acid and is a prostaglandin-2 precursor. α-linolenic acid is converted into EPA (prostaglandin-3 precursor) and in DHA (important cell membranes component). Omega-3 fatty acids give prostaglandin-3 and class-5 leukotrienes, with anti-inflammatory and vasodilatory activity. Omega-6 fatty acids give prostaglandin-2 and class-4 leukotrienes with a vasoconstrictive action, the activation of polymorphonucleated (PMN), and vessel permeability, so they have pro-inflammatory action.

Prostaglandins are synthesized by the prostate: cyclooxygenase generates series 1 from γ-linolenic acid, series 2 from arachidonic acid, and series 3 from EPA. These series of molecules are all similar but with different (sometimes opposite) activity. Some arachidonic acid derivates, such as leukotrienes, have local hormone activity but differ from the hormones because they are composed of fatty acids, synthesized from cell membranes, and their target tissue is the same by which they are produced.

The ruminant requirement for essential fatty acids (EFA) is not well defined. According to Holman, there is an EFA deficiency if the ratio between eicosatrienoic acid and eicosatetraenoic acid (derived from linoleic acid) in the enterocytes membranes is > 0.4. Even without a standard requirement, it is estimated that 88 mg/kg of body weight of linoleic acid is necessary for animal growth and maintenance.

In monogastric and human nutrition the omega-3 PUFA requirement is 0.2 g/day. In lactating dairy cow is really hard to establish the EFA exact requirement. The ingested unsaturated fatty acids are modified in the rumen through bio-hydrogenation, the progressive saturation of the chain by the hydrogen ions in this organ (Figure 1). This mechanism is necessary to protect rumen microflora from the PUFA antimicrobial activity. The bio-hydrogenation of dietary linoleic acid and linolenic acid in the rumen is 86% and 82%, respectively. Their secretion in milk is 30-60% of the intake and this amount is uncontrollable. The bio-hydrogenation result is stearic acid (C18:0, saturated).

Figure 1: Exemple of linoleic acid (C18:2) bio-hydrogenation in the rumen

Thanks to the short rumen transit time and the periodic emptying of the organ, we can find intermediates of saturation at the intestinal level and in the bloodstream, with positive effects on health. For example, conjugated linoleic acid (CLA) prevents human chronic pathologies such as atherosclerosis, inflammation, and coronary heart disease. On the other hand, this process is frequently associated with a low milk price because of an interference mechanism in the mammary gland. Just 2.5 g/day of trans-10, cis 12 C18:2 are enough to reduce the milk fat content by 25%. This mechanism saves energy for the animal: milk fat production takes energy and molecules from the Krebs cycle. To avoid the milk fat reduction, to save energy in a controlled way, or to increase CLA milk content, Cornell University suggests including in the diet a maximum of 600 g of PUFA, with no more than 70 g/day C18:1 trans. Timmons et al. (2001) indicated that standard dairy cow diets contain 1. 3-2.6% of linoleic acid and 0.3% of linolenic acid, as dry matter percentage.

Omega-3 fatty acids have a positive effect on bovine fertility: increased number and dimension of ovulatory follicles, increased plasma progesterone, reduced prostaglandin-2 (i.e. PGF2α) production. Fatty acids added to the diet during the transition period stimulate hepatic cholesterol secretion and increase the possibilities of the follicle and corpus luteum to produce estrogen and progesterone respectively. The reduction of PGF2α is due to the higher available linolenic acid: this acid and EPA are precursors of PGF3, produced competitively by the same enzymatic pathway of the series 2. At the same time, EPA and DHA inhibit the arachidonic acid synthesis and, consequently, of PGF2. Omega-3 fatty acids also inhibit monocytes cytokines production.

Nowadays, EFA are considered nutraceutical molecules with positive effects on animal and human health (Table 2). For example, the cell nuclear membrane has PPARs receptors that are α, β, or γ type and are activated by specific EFA. The alpha type activates genes that modulate lipid and lipoprotein metabolism inducing changes that are protective for the cardiovascular system. The gamma type activates the so-called “parsimony genes”, inducing a higher tissue response to insulin activity. This aspect can be very useful to face the insulin-resistance that many dairy cows present. To be really effective in using EFA as clinical nutrients (especially against low fertility and low immune function), their rumen degradation/saturation and the opposite activity that ω-3 and ω-6 fatty acids have on prostaglandin production must be considered. As a theoretical (but also practical) guideline, the supplementation of omega-6 during the close-up period and of omega-3 from the end of the puerperium until the new pregnancy can be very effective.

Conclusion

• NEFA are long-chain saturated fatty acids similar to the dietary ones (palmitic C16:0 and stearic C18:0 acid) if they are supplemented as saponified and hydrogenated sources.
• High plasma NEFA concentration gives a negative impulse to hypothalamic metabolism and ovarian follicles because it is related to NEBAL, not favorable for reproduction.
• The animal is not able to understand if the circulating NEFA are from its own lipid tissue or from the diet;
• A large amount of these NEFA is used by the udder to synthesize milk fat.
• NEFA, milk fat during the first weeks of lactation, and the single fatty acids are useful biomarkers for the cow energy balance and to manage the herd fertility. Milk protein is a good biomarker for amino acid balance.
• Milking dairy cow NEFA plasma concentration is < 0.6 mmol/l and their milk concentration is at least 0.85% for de-novo fatty acids (from C4:0 to C14:1), so the 18-30% of the total fatty acids. The mixed (C16:0-C16:1) and preformed (C18:0, C18:1, and C18:2) fatty acids are the 35-40%. Individual milk fat > 4.80% during the first month of lactation in Holstein cows is a biomarker of strong NEBAL, while milk protein < 2.80% indicates both NEBAL and NPO (negative protein balance).
• Omega-3 PUFA, such as ALA (C18:3 n-3), EPA (C20:5 n-3), and DHA (C22:6 n-3), improve fertility. They improve insulin tissue sensitivity increasing glucose uptake and reduce PGF production improving corpus luteum persistence. On the other hand, ω-3 PUFA are produced in the rumen after the bio-hydrogenation of dietary fatty acids and are responsible for the “low-fat milk syndrome” and the alteration of fatty acids ratios in milk. 2.5 g of trans-10 cis-12 C18:3 causes a 25% reduction in milk fat.
• Linseed oil is rich in ALA, while fish and seaweed contain EPA and DHA.
• If the integration of dairy cows diet with vegetable omega-3 PUFA (i.e. C18:3 n3) is required, the rumen-protected form is the best solution to avoid the reduction in milk fat and to obtain a correct intestinal absorption.

Table 2: Associations between different fatty acids, amino acids, urea, and bovine fertility.

For more information: marketing@vetagro.comOriginal article here: part #1 and #2.